The purpose of this project is to increase our understanding of the metabolism of retinoids. Such information must be obtained before new retinoids with greater activity in the reversal of preneoplasia in epithelial tissues can be rationally designed. The investigation is carried out along two basic lines: 1) The study of the in vitro metabolism of retinoic acid and synthetic retinoids in subcellular systems of target tissues as compared to non-target tissues, and 2) the study of the biochemical activation mechanisms of the synthetic retinoids.